Matrix Metalloproteinases and their natural inhibitors (TIMPs) regulate the dissolution of the extracellular matrix in growth and development, inflammatory and neoplastic diseases. The objective of this project is to investigate how cells orchestrate the episodic local dissolution of extracellular matrix by the orderly expression and function of MMPs and their inhibitors. Initially our studies are aimed at determining which MMPs are involved in the degradation of a single substrate (reconstituted fibrils of type I collagen) by a single cell type. To address this question we are employing a variety of molecular and cell biological approaches. Specifically we are pursuing mouse genetic approches (gene knock-out and replacement) in order to determine the function of various MMPs in extracellular matrix remodeling in health and disease.